Safety and Outcomes in Infants Born to Mothers Participating in Retosiban Treatment Trials: ARIOS Follow-up Study

Abstract

Objective Retosiban, an oxytocin receptor antagonist, was developed for treating spontaneous preterm labor (sPTL) in women with intact membranes. This ARIOS follow-up study aimed to characterize clinical safety, morbidity, and mortality of infants exposed to retosiban or comparator over 2 years.

Study Design ARIOS prospectively assessed outcomes in infants whose mothers received at least one dose of retosiban or comparator (placebo/atosiban) in two Phase 3 sPTL trials. Both trials were terminated prematurely owing to poor enrolment. Infants could be enrolled into ARIOS from 28 days after estimated due date until hospital discharge or up to 9 months (corrected age). An internally developed questionnaire detailing medical conditions, mortality and resource use (Child Health Inventory; CHI), Ages and Stages Questionnaire-3 (ASQ-3), Modified Checklist for Autism in Toddlers–Revised with Follow-Up, and Child Behavior Checklist for Ages 1.5 to 5 were completed remotely by parents or legal guardians at prespecified intervals. Serious adverse events (SAEs) were primarily captured via CHI. No comparative statistical analysis was conducted between treatment arms.

Results A total of 49 (86%) infants who had received retosiban and 49 (78%) infants who had received a comparator were enrolled in ARIOS. No deaths occurred during the study. Nine infants experienced SAEs: 6/49 (12.2%) infants in the comparators group and 3/49 (6.1%) in the retosiban group. Of the nine SAEs, seven were due to infections, three, and four in the retosiban and comparators groups, respectively. Based on ASQ-3 score, the incidence of neurodevelopmental delay at 18 and 24 months were 0/18 (0%) and 2/25 (8%) with retosiban and 7/22 (31.8%) and 3/21 (14.3%) with comparator, respectively.

Conclusion The current study showed no unexpected adverse outcome or impairment with retosiban based on safety monitoring and neurodevelopment assessments. No further follow-up is intended owing to the discontinuation of clinical development of retosiban.

Key Points

• There is a need for an effective and safe treatment for sPTL.

• ARIOS was a follow-up study of two Phase 3 trials in sPTL.

• There were no safety concerns with retosiban treatment.

• Slow recruitment led to termination of the Phase 3 trials.

Keywords

retosiban - preterm birth - oxytocin receptor antagonists - neurodevelopment

Note

M.P., N.H., D.M., and R.S. are employees and shareholders of GSK. J.M.P., K.B. and J.S. were employees of GSK at the time of the study and are shareholders of GSK. S.T. has provided and/or provides consultancy advice for commercial organizations such as GSK, Ferring, Pulsenmore, and Hologic, was a trustee of a charity that funds related research, is a trustee of other medical related organizations, and holds positions in RCOG and other organizations. E.O.C., M.P., D.M., K.B., N.H., G.S., R.S., J.S., and J.M.P. report other from GlaxoSmithKline and nonfinancial support from GlaxoSmithKline during the conduct of the study.

S.T. reports nonfinancial support from GlaxoSmithKline and Johnson & Johnson during the conduct of the study. Trialing a portable ultrasound device for PulseNmore. He is a Trustee of several charities including those that fund related research. He holds positions in the Royal College of Obstetricians and Gynaecologists and other organizations:

• EME Strategy Advisory Committee (2018–06–01 to 2019–06–01)

• EME Funding Committee Members (2015–12–01 to 2019–12–01)

• EME Funding Committee Sub-Group Remit and Comp Check (2019–11–01 to 2019–11–01)

• MRC Multimorbidity Board 2020

^* These authors contributed equally to this study.

Publikationsverlauf

Eingereicht: 15. März 2021

Angenommen: 28. Juni 2021

Artikel online veröffentlicht:
05. August 2021

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